The primary goal of this project is to develop MRI techniques for non-invasive detection of acute organ rejection following transplantation. Our current research focuses on two approaches to detecting rejection by MRI. The first involves tagging an NMR detectable agent to a rejection marker cell and the second involves the measurement of tissue perfusion in the transplanted organ as a marker of rejection. It is well known that the T-cell is the primary effector cell in acute graft rejection, and the homing of T-cells is a major field of transplantation immunology. T-cells isolated from rats are labeled with superparamagnetic iron oxide (SPIO) particles and injected to rats that have undergone organ transplantation. The transplanted organ is imaged by MRI at different time points post-transplantation to track the homing of the SPIO labeled T-cells to the site of rejection. It is also believed that other mediators of rejection, e.g. macrophages are also attracted to the site of rejection. We have just begun work to track the migration of SPIO labeled macrophages as well in the rat transplant model. To determine if changes in tissue perfusion can be used as a marker of organ rejection, perfusion images of rat kidneys are obtained in a rat renal transplant model. Quantitative perfusion images are obtained in rats with one transplanted and one native kidney, using the arterial spin labeling technique developed in this Center. Preliminary results indicate a significant decrease in perfusion in the transplanted kidney, as compared to the native kidney. Control experiments are under way to isolate the immunological response from any possible surgical complications due to the transplantation.